Factors influencing the pattern of emergence of several recently recognized tick-borne pathogens throughout the northern temperate regions of the world may be related to biological or environmental factors that limit the distribution of Ixodes ricinus-complex ticks. Previously, we identified factors influencing transmission dynamics of Lyme disease spirochetes. Studies of reservoir potential helped identify the principal zoonotic hosts of Borrelia burgdorferi and models were developed to predict entomologic risk. Now, we will expand those studies to include other potentially confounding infections apparently vectored by Ixodes scapularis in the northeastern US. The rodent piroplasm Babesia microti, and closely-related organisms may be more broadly distributed than previously thought yet human disease remains relatively rare. There may be factors further limiting human infection with this agent even within the range of vector-competent ticks. Human ehrlichiosis now has been found in two forms, monocytic (HME) and granulocytic (HGE). Although the causative agent of HME is more prevalent in the southern United States, HGE has only been found in northern regions. The ecologies of both erhlichial agents are poorly understood. Identification of vectors and reservoir hosts is still needed to help understand the potential distribution of human-infecting erhlichiae in the northern US. Thus, the proposed research will increase knowledge about those factors contributing to emergence of human disease vectored by ticks. Specifically, we will: (1) determine factors that regulate the distribution of deer ticks; (2) assess this tick's vector potential for a variety of zoonotic pathogens; (3) examine effects of vector density on zoonotic maintenance of L. scapularis-associated pathogens; and (4) evaluate determinants of human infection risk for Lyme disease, babesiosis and erhlichiosis. Knowledge of the principles affecting disease emergence is essential in planning strategies to prevent, treat and control disease. By building on the progress made previously by this project, we are well positioned to move rapidly towards our goals.